Short article: Influence of regulatory NLRC5 variants on colorectal cancer survival and 5-fluorouracil-based chemotherapy
Language English Country Great Britain, England Media print
Document type Journal Article
- MeSH
- Time Factors MeSH
- Adult MeSH
- Phenotype MeSH
- Fluorouracil administration & dosage adverse effects MeSH
- Gene Frequency MeSH
- Genetic Predisposition to Disease MeSH
- Genetic Association Studies MeSH
- Intracellular Signaling Peptides and Proteins genetics MeSH
- Polymorphism, Single Nucleotide * MeSH
- Kaplan-Meier Estimate MeSH
- Colorectal Neoplasms drug therapy genetics mortality pathology MeSH
- Middle Aged MeSH
- Humans MeSH
- Biomarkers, Tumor genetics MeSH
- Disease-Free Survival MeSH
- Proportional Hazards Models MeSH
- Antineoplastic Combined Chemotherapy Protocols adverse effects therapeutic use MeSH
- Risk Factors MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Neoplasm Staging MeSH
- Case-Control Studies MeSH
- Treatment Outcome MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Czech Republic MeSH
- Names of Substances
- Fluorouracil MeSH
- Intracellular Signaling Peptides and Proteins MeSH
- Biomarkers, Tumor MeSH
- NLRC5 protein, human MeSH Browser
BACKGROUND: NLRC5 is an interferon γ-inducible protein, which plays a role in immune surveillance with a potential influence on cancer survival. OBJECTIVE: We aimed to evaluate the effect of potential regulatory variants in NLRC5 on overall survival and survival after 5-fluorouracil (5-FU)-based therapy of colorectal cancer (CRC) patients. PATIENTS AND METHODS: We carried out a case-only study in a Czech population of 589 cases; 232 received 5-FU-based therapy. Eleven variants within NLRC5 were selected using in-silico tools. Associations between polymorphisms and survival were assessed by Cox regression analysis adjusting for age at diagnosis, sex, and TNM stage. Survival curves were derived using the Kaplan-Meier method. RESULTS: Two variants showed a significant association with survival. All patients and metastasis-free patients at the time of diagnosis (pM0) who were homozygous carriers of the minor allele of rs27194 had a decreased overall survival (OSall and OSpM0) and event-free survival (EFSpM0) under a recessive model (OSall P=0.003, OSpM0 P=0.005, EFSpM0 P=0.01, respectively). OS was also decreased for all patients and for pM0 patients who carried at least one minor allele of rs289747 (OSall P=0.03 and OSpM0 P=0.003, respectively). Among CRC patients, who underwent a 5-FU-based adjuvant regimen, rs12445252 was associated with OSall, OSpM0 and EFSpM0, according to the dosage of the minor allele T (OSall P=0.0004, OSpM0 P=0.0001, EFSpM0 P=0.008, respectively). CONCLUSION: Our results showed that polymorphisms in NLRC5 may be used as prognostic markers of survival of CRC patients, as well as for survival in response to 5-FU treatment.
Biomedical Centre Faculty of Medicine Pilsen
Center for Primary Health Care Research Clinical Research Center Lund University Malmö Sweden
Division of Molecular Genetic Epidemiology German Cancer Research Center Heidelberg
Institute of Biology and Medical Genetics 1st Faculty of Medicine
Molecular and Genetic Epidemiology Italian Institute for Genomic Medicine Turin Italy
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